Finding new treatments for those who need them most

10 Aug 2020

For some types of childhood cancer, such as acute lymphoblastic leukaemia, treatments have come a long way and survival rates are much higher than they used to be. But for some other types of cancer, cure remains elusive. New treatment options are desperately needed for children with these cancers.

IMT in children

One cancer which can prove difficult to treat is a type of sarcoma called IMT, which stands for inflammatory myofibroblastic tumours. IMT is quite rare, but when it does occur, it’s usually in a child or teenager. Chemotherapy tends not to work well in IMT, so treatment is often limited to surgery.

Drugs that have been shown to work well in some children with IMT over the last decade are ‘ALK inhibitors.’ These inhibitors are a type of targeted therapy − a therapy that has been developed to aim at a particular target in cancer cells. In this case, the target is ALK, which is one protein that makes the cancer cell different from a normal cell.

Unfortunately, some children with IMT who are given ALK inhibitors later relapse, and when their cancer comes back, it’s resistant to treatment. Many of these children are found to have a very aggressive subtype of the disease, called ‘ALK-re-arranged epithelioid inflammatory myofibroblastic sarcoma’ (eIMS). A different treatment option is desperately needed for these children.

What can we do about eIMS?

In the past, scientists haven’t been able to make a lot of progress in coming up with a solution for children with eIMS. One of the main stumbling blocks has been a lack of appropriate ‘experimental models’ that researchers can use to test potential new treatments.

When scientists think they may have found a treatment for a particular type of cancer, the first step is usually to test the treatment in cancer cells grown in the laboratory. The next step is to test the treatment in a living model of disease. Often, this means testing in mice that have been specially bred to grow cancer cells taken from actual patients. Called patient-derived xenografts, or PDXs, these models effectively mimic disease in humans. Testing drugs in these models is the closest thing to testing them in people, which only ever happens in a clinical trial after a drug has already been shown to be safe and effective in living models of disease.

At Children’s Cancer Institute, PhD student Ashleigh Fordham and colleagues have made what we believe to be the world’s first living models of eIMS. Two new models have been created − purified cells grown in the laboratory, and mouse models − both of which can be used to test potential therapies for children with this disease.

A new way to treat IMT

Under the guidance of her PhD supervisors, Ashleigh recently used the new models to test a novel treatment strategy for eIMS. And in recognition of this world-first, her findings have just been accepted for publication in one of the world’s leading cancer research journals, the British Journal of Cancer.

The treatment strategy that Ashleigh tested in the models is a combination of two targeted therapies: an ALK inhibitor together with ‘CD30-targeted therapy’. CD30-targeted therapy targets a protein called CD30 found on the surface of certain cancer cells, and is currently being used to treat a type of cancer called lymphoma.

Posing the question ‘Could this therapy work for children with eIMS too?’, Ashleigh tested it in her newly created mouse model. Excitingly, her results showed that it worked extremely well. When CD30-targeted therapy (a drug called brentuximab vedotin, or BV) was given in combination with an ALK inhibitor (crizotinib or ceritinib) to the mice, their tumours shrank significantly, and survival was prolonged.

‘I really hope this treatment can be fast-tracked to clinical trial in children with eIMS’, says Ashleigh. ‘Children who relapse with this disease desperately need a new treatment, and this combination therapy might be able to help them.’

This research was made possible through funding awarded by The Rory Williams Fund, the Australian Sarcoma Study Group (Xavier Krikori Grant), the Kids Cancer Alliance, and the National Health and Medical Research Council.